This invention relates generally to the field of time dispersive spectroscopy. More particularly, methods and apparatus are provided for determining the chemical constituents of a sample predicated on separating the constituents on the basis of their differing velocities. The present invention includes time dispersive devices such as ion mobility spectrometers (IMS), plasma chromatography, time-of-flight (TOF) mass spectrometers, capillary gas chromatographs and the like.
Presently, there are four methods of time dispersive spectrometry. The first is the xe2x80x9csingle scanxe2x80x9d method which involves opening an entrance gate for a short period of time to admit ions into a drift region of a spectrometer. The entrance gate is typically left open for approximately 0.2 milliseconds before it is closed thereby blocking further ions from entering the drift region. The pulse of ions admitted during the period the entrance gate is open move down the drift region under the force of an electric field and countercurrent to a drift gas. In the single scan method there is no exit gate and the ions strike directly onto an ion detector. The ion detector is connected to an oscilloscope which is used to monitor the output signal of the ion detector. The single scan method suffers from high noise levels in the detector output signal and accordingly cannot be used for high resolution chromatographic separations.
The second method of time dispersive spectroscopy is termed the xe2x80x9csignal averagingxe2x80x9d method. The signal averaging method again involves opening the entrance gate for a short period of time to allow a pulse of ions to pass into the drift region and be propelled therethrough under the force of the electric field. The ions again strike directly upon the ion detector, as in the single scan method. In the signal averaging method, many repetitions of single scans are performed and recorded, such as with a computer. Five hundred to 1,000 repetitions are often required to provide statistically acceptable signal to noise levels. Such numerous repetitions typically require a minimum of 10 to 20 seconds to perform thereby rendering the method unacceptable for high resolution chromatographic separation of sample constituents on an on-line basis.
The third method of time dispersive spectroscopy is termed the xe2x80x9cmoving second gatexe2x80x9d method. Such method is used with ion mobility spectrometers having an exit gate which is located at the end of the drift region prior to the ion detector. A pulse of ions are admitted through the entrance gate and propelled through the drift region under the force of the electric field. The second or exit gate positioned at the end of the drift region selectively opens for a short period of time usually equal to the time the entrance gate is opened. The time delay between opening of the entrance gate and subsequent opening of the exit gate thus allows only ions having transit times approximately equal to such time delay to pass through the exit gate and onto the ion detector. The strength of the measured signal indicates the quantity of ions having such transit time. The time delay between the opening of the entrance gate and the opening of the exit gate is varied over a range of relevant transit times and a large number of experimental ion pulses are needed in order to generate acceptable data indicating ion quantity (signal strength) as a function of transit time. Because of the large number of different delay times which must be tested, the amount of time necessary to test the full spectrum of transit times with sufficient specificity, accuracy, and to obtain acceptable signal to noise levels thus requires testing for a minimum of one or two minutes. Thus, the moving second gate method is also not acceptable for analyzing constituents on an on-line basis, especially if the amount of sample material is limited.
The fourth method of time dispersive spectroscopy is known as the Fourier transform, or xe2x80x9cFTxe2x80x9d, method as described by Knorr, et al in U.S. Pat. No. 4,633,083 and xe2x80x9cFourier Transform Ion Mobility Spectrometerxe2x80x9d by Knorr et al in Anal Chem. Vol. 57, 402-406 (1985), both of which are incorporated by reference herein. In the FT method, the ions are admitted into a drift region in pulses by opening an entrance gate for variable short periods of time termed gate open or ion admission periods. Consideration of only those ions exiting the drift region during gate open periods can be accomplished using an exit gate which simultaneously opens and closes with the opening and closing of the entrance gate, thereby allowing ions to be detected which exit during the entrance gate open periods and excluding ions exiting during complementary entrance gate closed periods. Simultaneous opening and closing of the entrance and exit gates is controlled by a gating function over a range of frequencies to produce associated ranges of times for the gate open periods and gate closed periods. Only ions which exit the drift region during the entrance gate open periods are considered in the subsequent analysis. Data is recorded in the form of the ion detection signal as a function of the variable gate frequency. For each type of ion there are a series of maxima in the ion detection signal when the ion pulses are in phase with the gating function. Correspondingly, for each ion there are a series of minima in ion detection signal when the ion pulses are out of phase with the gating function. The ion pulses are thus said to interfere or form an interference function with the gating function. Data in the form of ion detection signal as a function of frequency can thus be plotted as an interference function or interferogram displaying such maxima and minima. The interference function contains information on the quantity of ions having various transit times. This information can be transformed from the frequency domain to the time domain using a suitable mathematical transform such as a Fourier transform, or xe2x80x9cFTxe2x80x9d.
There are two clear advantages of FT method compared to the other methods of operation previously described. First, because the duty cycle of the FT method is 25 times that of the single scan method, the FT method offers up to five times the signal to noise ratio(S/N). Second, the peak asymmetries due to reactions in the drift tube simply disappear in the FT method. This occurs because the FT method uses a constant frequency difference between the ion-carried chirp and the second gate to generate a constant beat frequency. Ions that react during their transit of the drift region have no well-defined drift time and give incoherent signals at the second gate, adding only to the DC signal level and random background noise.
Nevertheless, there remain at least three problems with the FT method of time dispersive spectroscopy. First, in addition to different gating electronics associated with the spectrometer, the FT method has required a drift tube of basically different construction than most of the more conventional time dispersive devices making it difficult for users to use the method. Secondly, it has been difficult to make direct comparisons of actual relative performance of the FT method with existing ion mobility spectra because the differing designs have required either awkward, time consuming, and contamination producing component interchanges or use of drift tubes having two gates and an aperture grid, with the attendant signal loss due to a third screen. Partly for these reasons, there has been no S/N comparisons which might encourage wider adoption of the FT method. Thirdly, having two physical gates within the drift region reduces the duty cycle from a theoretical maximum of 50% to 25% and the potential enhancement of S/N from seven to five.
Additionally, none of the existing four methods of time dispersive spectroscopy described above make the most efficient use of the available ions. Typical entrance gate pulse durations of 0.2 milliseconds with recurrent pulses every 20 milliseconds allow only one percent of the available ions from the sample to pass into the drift region. This small proportion of the available ions admitted into the drift region is further reduced in the moving second gate method by the selective opening and closing of the exit gate for approximately similar periods of time. This results in an average of only one percent of the ions admitted through the entrance gate passing through the exit gate and onto the ion detector. The resulting 1.0 percent utilization of available ions allows only a relatively weak signal to be developed at the ion detector, thus causing a poor signal to noise ratio. This requires that multiple scans be averaged to achieve adequate signal-to noise.
The present invention provides a novel method and apparatus for chemical analysis by time dispersive spectrometry. Unlike previous methods and apparatus, the present invention does not require the use of two physical gates within drift region of the time dispersive spectrometer. More specifically, the present invention employs modulation of the detection signal and an FT mode of operation without modifying conventional time dispersive devices to include a second physical gate. Consequently, the results obtained by the present invention are directly comparable to single gated time dispersive devices. Moreover since only a single physical gate is employed, the present invention is able to achieve higher signal-to-noise ratios than current FT devices employing two physical gates as well as better utilize the amount of sample available.
The present invention provides novel methods and approaches for identifying chemical constituents of a multi-component sample using time dispersive spectrometry. In particular, the present invention more effectively utilizes limited sample materials available for analysis. Additionally, the present invention achieves higher signal to noise ratios resulting in more accurate analysis of chemical constituents of a sample.
In one embodiment of the present invention, the flow of an ionized sample into a drift region of a time dispersive spectrometer is modulated; ions traversing the drift region of a time dispersive device are detected and an ion detection signal is obtained; and the ion detection signal is modulated to obtain a frequency domain representation of the chemical constituents of the sample. Further, the frequency domain representation of the chemical constituents can be transformed into a time-domain representation of the chemical constituents of the sample, both qualitative and quantitative analyses of the constituents can be performed on the modulated ion detection signal.
In another embodiment of the invention, a time dispersive spectrometer includes a first physical gate for controlling the flow of an ionized sample into a drift region of the time dispersive spectrometer and an ion detector for producing an ion detection signal after the ions have traversed the drift region. The time dispersive spectrometer further includes a modulator for controlling both the flow ions past the first physical gate and modulating the ion detection signal to obtain a frequency domain representation of the chemical constituents of the sample. The apparatus further includes means for transforming the frequency domain representation into a time domain representation of the constituents of the sample.